Article

Foxp3+ regulatory T cells: Differentiation specification subphenotypes

Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA.
Nature Immunology (Impact Factor: 24.97). 08/2009; 10(7):689-95. DOI: 10.1038/ni.1760
Source: PubMed

ABSTRACT Regulatory T cells (T(reg) cells) characterized by expression of the transcription factor Foxp3 play a key role in immune homeostasis. Rather than a monomorphic population strictly determined by Foxp3 as a 'master regulator', the emerging view is one of T(reg) cells as a population with many levels of complexity. Several regulatory factors partake in the control of their transcriptional 'signature', with Foxp3 being a key regulator but insufficient and unnecessary to specify all aspects of the lineage. Distinct subphenotypes of Foxp3+ T(reg) cells are found in different anatomical locations. Some subphenotypes specifically control different facets of effector T cell function and, perhaps surprisingly, share transcriptional control elements with the very cells they regulate. This review will focus on these novel aspects of T(reg) cell diversity.

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    • "FoxP3 + regulatory T (Treg) cells restrain the immune responses to self-antigens, pathogens, allergens, and commensal microorganisms (Feuerer et al., 2009; Josefowicz et al., 2012a). Treg cells are produced in the thymus (tTreg) but may also be generated in the periphery (pTreg) or in vitro (iTreg) by conversion of naive conventional T (Tconv) cells (Curotto de Lafaille and Lafaille , 2009; Yadav et al., 2013). "
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    • "Cells which survive the selection are exported to the periphery as CD4 + helper or CD8 + cytotoxic single positive (SP) naïve cells where they are ready for antigenic challenge and differentiation into effector cells (Stritesky et al., 2012). Importantly, besides these two major cell subsets, regulatory T cells are also generated which play a crucial role in suppressing and controlling autoimmunity (Feuerer et al., 2009). The selection process is extremely important in generating a functional T cell repertoire and deficiencies in this process may lead to defective immune tolerance and autoimmunity (von Boehmer and Melchers, 2010). "
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    • "Under these conditions, anti-CD28 stimulation supported the production of endogenous IL-2. In contrast, other studies showed that costimulation through CD28 can inhibit aTreg differentiation, most likely via the PI3K– mTOR pathway (Feuerer et al., 2009; Merkenschlager and von Boehmer, 2010). Therefore, the use of anti-CD28 for aTreg generation introduces additional complexity that may be difficult to define. "
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